Mitonucleon-initiated dome formation involves structural changes
occurring over a 20 to 24 hour period in monolayer cells induced by a serum
factor. The earliest observable change is the fusion of monolayer cells into a
syncytium in which nuclei aggregate and become surrounded by a membrane that
stains for endogenous biotin. Each of these structures is further surrounded by
a fraction of the mitochondria that arise in the syncytium following initiation
of dome formation. The mitochondria fuse around the chromatin aggregate in a
structure we have called a mitonucleon. Within mitonucleons, a gaseous vacuole
is generated that can be seen in protrusions of the apical membrane pressuring
chromatin into a pyknotic state. Eventually that pressure, together with
whatever enzymatic changes have occurred in the bolus of chromatin, results in
DNA fragmentation. The fragments drawn out through the syncytium by a unipolar
spindle are arrayed in a configuration that appears open both to epigenetic
changes and to DNA repair and replication by polyteny. The fragmented DNA
stretched across the syncytial space, hardly detectable by light microscopy,
becomes visible approximately half way through the differentiation as the
filaments thicken in what looks like replication by polyteny. This “recycling”
of attached monolayer cells into detached dome cells must include DNA
replication since the number of cells in the resulting domes is greater than
the number of monolayer cells by 30% or more. The resulting DNA associates into
a mass of chromatin which will “segment” into polyploid structures and then
into what appear to be diploid nuclei over a period of 2 to 4 hours. When the
layer of nuclei has filled the syncytium, the nuclei are cellularized, forming
dome cells rising up from the monolayer and arching over a fluid cavity. Dome
cells can extend into gland-like structures by the same mitonucleon dependent
amitotic process observed in dome formation. Some of the characteristics of
this process resemble the amitotic process of schizogony among single-celled
eukaryotic parasites of the apicomplexan phylum. Mitonucleon initiated amitotic
proliferation results in synthesis of dozens of dome cell nuclei in a period of
20 to 24 hours, so it is much more efficient than mitosis. Cells generated by
this process and their progeny would also not be sensitive to agents that
inhibit mitosis suggesting that the process, as an alternative to mitosis,
might be activated in cancers that become resistant to some cytotoxic drugs.
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